Treatment of colitis ulcerosa

ABSTRACT

Colitis ulcerosa is treated according to the invention by administering to the patient suffering from such condition an effective dose of penicillamine. The preferred penicillamine because of its low toxicity is D-penicillamine. All types of administration are suitable, including oral administration and administration by injection. The actual dosage depends upon the extent of the condition. Orally the dose may be as little as 0.6 g per day and as high as 2.4 g per day, and even higher for short periods. By injection the dose may be as little as 0.5 g and as high as 1.5 g per day.

United States Patent [1 1 Kludas Jan. 29, 1974 TREATMENT OF COLITISULCEROSA [75] Inventor: MartinKludas, Berlin, Germany [73] Assignee:Heyl & Co., Chem.-Pharm. Fabrik, Berlin, Germany [22] Filed: July, 3,1972 [21] Appl. No.: 268,675

Related US. Application Data [62] Division of Ser. No. 81,626, Oct. 16,1970.

[52] US. Cl. 424/319 [51] Int. Cl A6lk 27/00 [5 8] Field of Search424/319 [5 6] References Cited OTHER PUBLICATIONS Merck Index, 8thEdition, 1968, Merck & Co., Inc., Rahway, NJ. page 789.

Douland, Medical Dictionary, 1938, page 335.

Primary Examiner-Jerome D. Goldberg Attorney, Agent, or Firm-Harold D.Steinberg et al.

57 ABSTRACT Colitis ulcerosa is treated according to the invention byadministering to the patient suffering from such condition an effectivedose of penicillamine. The pre ferred penicillamine because of its lowtoxicity is D- penicillamine. All types of administration are suitable,including oral administration and administration by injection. Theactual dosage depends upon the extent of the condition. Orally the dosemay be as little as 0.6 g per day and as high as 2.4 g per day, and evenhigher for short periods. By injection the dose may be as little as 0.5g and as high as 1.5 g per day.

5 Claims, No Drawings TREATMENT OF COLITIS ULCEROSA CROSS REFERENCE TORELATED APPLICATION This application is a divisional of my copendingapplication Ser. No. 81,626 filed Oct. 16, 1970, for Treatment ofScleroses and Conditions of Autoimmunization.

BACKGROUND OF THE INVENTION Cortisone therapy must be considered asuseless in the treatment of colitis ulcerosa chiefly because it causesundesirable side effects such as Cushings Syndrome or osteoporosis.

SUMMARY OF THE INVENTION Generally speaking, in accordance with thepresent invention, a subject suffering from colitis ulcerosa isadministered an effective dose of penicillamine, particularlyD-penicillamine.

The present invention further provides for the treatment of colitisulcerosa wherein a highly effective action is achieved with minimumtoxicity and lack of undesired side effects.

Other objects and advantages of the present invention will be apparentfrom further reading of the specification and of the appended claims.

With the above and other objects in view, the present invention mainlycomprises the treatment of colitis ulcerosa by administering to thepatient suffering from the same an effective amount of penicillamine.

Although the L-isomer and the DL-isomer of penicillamine are both activefor the same purposes as the D penicillamine, their toxicity is so muchhigher than D- penicillamine, that as a practical matter the D-penicillamine is used for the purposes of the present invention.

The use of penicillamine in the treatment of provides considerableadvantages in that the penicillamine in contrast to otherimmunosuppressive drugs acts extracellular, so that it is less toxic andthe possibility of particular side effects is avoided.

The dosage of the penicillamine of course depends upon the extent of thecondition being treated. Thus, the higher the degree of cross linkingand the more insoluble collagens, the higher the dosage of thepenicillamine required to achieve the therapeutic effect. Likewise, theduration of administration is also dependent upon the degree of crosslinking and amount of scar formation.

In most cases a suitable dosage program would be the administration of0.3 g of D-penicillamine for one week, then increasing the dosage by 0.3g per day for an additional week until the full dosage of 1.8 g per dayis arrived at. This dosage program is most desired in order to avoid anyside effects.

After achieving the therapeutic effect, the dosage can be reduced to 0.6g per day and then later completely eliminated.

In particularly difficult conditions, it is possible to increase thedaily dosage for a short time up to a daily dosage of 5 g ofD-penicillamine.

It is generally satisfactory to administer the penicillamine orally. Inthe case of highly advanced conditions it may be advisable to use ahigher dosage, particularly at the beginning of the treatment, and insuch case a dosage of l g of the D-penicillamine intravenously isadvantageous. 9

The penicillamine may be used for the purposes of the present inventionin the form of its free base or in the form of an acid addition saltthereof, particularly of a mineral acid, such as hydrochloric acid.

In the preparation of products for oral administration or foradministration by injection it is desirable to avoid the presence ofoxygen which causes deterioration of the pharmaceutical action as aresult of autoxidation with formation of penicillamine-disulfide. Inorder to avoid contact with the air, it is advisable to provide the oralform in air-tight, sealed hard gelatin capsules or in air-tight tabletform.

For parenteral administration the penicillamine may be in the form of asolution, however in a special form which minimizes the decomposition ofthe penicillamine and also does not harm the patient upon injectionthrough the skin. Since the mineral acid addition salt of penicillamine,such as D-penicillamine-hydrochloride are quite acid (pl-I of about 2),the solution of the acid addition salt in water for injection shouldhave buffers added thereto in order to increase the pH of the solution.Among the suitable buffers for this purpose are tris (hydroxyamino)methane, borox-succinic acid buffer of Kolthoff, citrate buffer ofSorensen, citric acid-phosphate buffer of Mcllvaine, glycol buffer ofSorensen, potassium biphthalate buffer of Clark and Lubs, standardacetate buffer of Michaelis and others.

For oral administration, the minimum daily dose is generally about 0.6 gwith a maximum of about 2.4 g per day, the preferred oral administrationbeing by means of tablets each containing 0.3 g, so that the dailyadministration of tablets is between 2 and 8 tablets per day. Asindicated previously, however, for short periods of time, and in casesof severe conditions, the daily dose may be as high as 5 g.

In the case of parenteral administration, which can be intraveneous orintramuscular, with intravenous being preferred because of greatercertainty of pharmacological action, the unit dose is between about 0.5g of D-penicillamine and 1.5 g. This dose is preferably administered asone injection per day. The preferred daily individual dose is about 1.0g of D-penicillamine.

Penicillamine may be used in accordance with the present invention notonly in the treatment of human beings, but also in animals.

The oral dosage of penicillamine in the treatment of dogs and cats isgenerally between about 20 and 30 mg/kg of body weight, and preferablyabout 25 mg/kg. The parenteral dosage is between about 10 and 20 mg/kgand preferably about 15 mg/kg of body weight.

In the case of horses and cattle, the oral daily dosage is generallybetween about 15 and 25 mg/kg and preferably about 20 mg/kg of bodyweight, the parenteral dosage being between about 5 and 15 mg/kg andpreferably about 10 mg/kg of body weight.

DESCRIPTION OF PREFERRED EMBODIMENTS The following example is given tofurther illustrate the present invention. The scope of the invention isnot, however, meant to be limited to the specific details of theexample.

EXAMPLE A male patient suffering from colitis ulcerosa is treated byadministration of D-penicillamine orally in a daily dose of 0.3 g (onetablet containing 0.3 g penicillamine per day). The dosage is continuedfor several weeks after which the pateint is found to have clinicallyimproved from the colitis ulcerosa condition.

While the invention has been illustrated in particular with respect to aparticular course of treatment, it is apparent that variations andmodifications of the invention can be made.

What is claimed is:

1. Method of treating a patient suffering from colitis ulcerosa whichcomprises administering to said patient an anti-colitis ulcerosaeffective amount of D- to claim 1 wherein the mode of

2. Method according to claim 1 wherein the mode of administration is oral.
 3. Method according to claim 2 wherein the daily dose is between about 0.6 g and 2.4 g.
 4. Method according to claim 1 wherein the mode of administration is parenteral.
 5. Method according to claim 4 wherein the daily dose is between about 0.5 g and 1.5 g. 